TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34327	103204;103205;103206	chr2:178533636;178533635;178533634	chr2:179398363;179398362;179398361
N2AB	32686	98281;98282;98283	chr2:178533636;178533635;178533634	chr2:179398363;179398362;179398361
N2A	31759	95500;95501;95502	chr2:178533636;178533635;178533634	chr2:179398363;179398362;179398361
N2B	25262	76009;76010;76011	chr2:178533636;178533635;178533634	chr2:179398363;179398362;179398361
Novex-1	25387	76384;76385;76386	chr2:178533636;178533635;178533634	chr2:179398363;179398362;179398361
Novex-2	25454	76585;76586;76587	chr2:178533636;178533635;178533634	chr2:179398363;179398362;179398361
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-161
• Domain position: 70
• Structural Position: 149
• Q(SASA): 0.0927
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
D/N	None	None	0.235	N	0.353	0.563	0.372087925617	gnomAD-4.0.0	1.59099E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
D/A	0.9588	likely_pathogenic	0.946	pathogenic	0.158	Stabilizing	0.993	D	0.861	deleterious	D	0.52984906	None	None	N
D/C	0.987	likely_pathogenic	0.9856	pathogenic	0.174	Stabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
D/E	0.9211	likely_pathogenic	0.9084	pathogenic	-0.78	Destabilizing	0.977	D	0.619	neutral	N	0.508920421	None	None	N
D/F	0.9935	likely_pathogenic	0.9891	pathogenic	0.528	Stabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
D/G	0.966	likely_pathogenic	0.9584	pathogenic	-0.318	Destabilizing	0.955	D	0.751	deleterious	D	0.547535241	None	None	N
D/H	0.9623	likely_pathogenic	0.9536	pathogenic	0.064	Stabilizing	0.999	D	0.861	deleterious	N	0.503071071	None	None	N
D/I	0.9912	likely_pathogenic	0.9864	pathogenic	1.446	Stabilizing	0.998	D	0.899	deleterious	None	None	None	None	N
D/K	0.9911	likely_pathogenic	0.9894	pathogenic	-0.159	Destabilizing	0.995	D	0.827	deleterious	None	None	None	None	N
D/L	0.9898	likely_pathogenic	0.9863	pathogenic	1.446	Stabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
D/M	0.9935	likely_pathogenic	0.9927	pathogenic	1.998	Stabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
D/N	0.8096	likely_pathogenic	0.7937	pathogenic	-0.901	Destabilizing	0.235	N	0.353	neutral	N	0.512794761	None	None	N
D/P	0.9988	likely_pathogenic	0.9986	pathogenic	1.047	Stabilizing	0.999	D	0.854	deleterious	None	None	None	None	N
D/Q	0.9864	likely_pathogenic	0.9849	pathogenic	-0.5	Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
D/R	0.9921	likely_pathogenic	0.991	pathogenic	-0.274	Destabilizing	0.995	D	0.888	deleterious	None	None	None	None	N
D/S	0.9099	likely_pathogenic	0.8908	pathogenic	-1.239	Destabilizing	0.966	D	0.664	neutral	None	None	None	None	N
D/T	0.9744	likely_pathogenic	0.9612	pathogenic	-0.797	Destabilizing	0.995	D	0.831	deleterious	None	None	None	None	N
D/V	0.9766	likely_pathogenic	0.9665	pathogenic	1.047	Stabilizing	0.997	D	0.891	deleterious	D	0.548295709	None	None	N
D/W	0.9988	likely_pathogenic	0.9983	pathogenic	0.417	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
D/Y	0.9573	likely_pathogenic	0.9422	pathogenic	0.735	Stabilizing	1.0	D	0.909	deleterious	D	0.530102549	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.